Inhalable resveratrol-cyclodextrin complex loaded biodegradable nanoparticles for enhanced efficacy against non-small cell lung cancer

Wang, Xuechun; Parvathaneni, Vineela; Shukla, Snehal K.; Kulkarni, Nishant S.; Muth, Aaron; Gupta, Vivek

doi:10.1016/j.ijbiomac.2020.07.124

Cited by 71 publications

(29 citation statements)

References 66 publications

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“…Plain BDQ, however, did not exert any significant cell death at tested concentrations, and IC 50 values could not be determined, suggesting the need for higher doses. Similar results were observed in case of cyclodextrin inclusion complexes of erlotinib and resveratrol, as reported earlier by our research group [ 14 , 51 ]. In vitro studies to establish safety of optimized cyclodextrin formulation was performed on human epithelial kidney 293 cell line HEK-293.…”

Section: Resultssupporting

confidence: 92%

“…Other studies report the ability of CDs to enhance pulmonary absorption where relative impermeability of the lungs to several drugs is posing a major obstacle after pulmonary delivery [50]. deposition is greater for polydisperse aerosols compared to monodisperse aerosols, as seen in Figure 8B [51]. The FPF, also called the respirable fraction, was calculated to be 83.3 ± 3.8%, which suggests excellent aerosolization performance and that much of the dose will be deposited in the respiratory airways.…”

Section: In Vitro Aerosol Performancementioning

confidence: 85%

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Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Parvathaneni

Elbatanony

Goyal

et al. 2021

IJMS

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There is growing evidence that repurposed drugs demonstrate excellent efficacy against many cancers, while facilitating accelerated drug development process. In this study, bedaquiline (BDQ), an FDA approved anti-mycobacterial agent, was repurposed and an inhalable cyclodextrin complex formulation was developed to explore its anti-cancer activity in non-small cell lung cancer (NSCLC). A sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD) was selected based on phase solubility studies and molecular modeling to prepare an inclusion complex of BDQ and cyclodextrin. Aqueous solubility of BDQ was increased by 2.8 × 103-fold after complexation with SBE-β-CD, as compared to its intrinsic solubility. Solid-state characterization studies confirmed the successful incorporation of BDQ in the SBE-β-CD cavity. In vitro lung deposition study results demonstrated excellent inhalable properties (mass median aerodynamic diameter: 2.9 ± 0.6 µm (<5 µm) and fine particle fraction: 83.3 ± 3.8%) of BDQ-CD complex. Accelerated stability studies showed BDQ-CD complex to be stable up to 3 weeks. From cytotoxicity studies, a slight enhancement in the anti-cancer efficacy was observed with BDQ-cyclodextrin complex, compared to BDQ alone in H1299 cell line. The IC50 values for BDQ and BDQ-CD complex were found to be ~40 µM in case of H1299 cell line at 72 h, whereas BDQ/BDQ-CD were not found to be cytotoxic up to concentrations of 50 µM in A549 cell line. Taken together, BDQ-CD complex offers a promising inhalation strategy with efficient lung deposition and cytotoxicity for NSCLC treatment.

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Section: Resultssupporting

confidence: 92%

Section: In Vitro Aerosol Performancementioning

confidence: 85%

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Parvathaneni

Elbatanony

Goyal

et al. 2021

IJMS

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“…This is indicative of a longer pulmonary retention of RES, with a slower entry into the systemic blood circulation compared to an intravenously dosed RES solution [ 17 ]. Wang et al [ 18 ] demonstrated how the water solubility of RES may be increased 66-fold by aerosolization with a sulfobutylether-β-cyclodextrin (CD-RES) complex loaded onto polymeric nanoparticles [ 18 ]. In the in vitro experiments, CD-RES nanoparticles demonstrated improved cellular uptake, cytotoxicity, and apoptosis compared to RES (while antioxidant activity was preserved) [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Wang et al [ 18 ] demonstrated how the water solubility of RES may be increased 66-fold by aerosolization with a sulfobutylether-β-cyclodextrin (CD-RES) complex loaded onto polymeric nanoparticles [ 18 ]. In the in vitro experiments, CD-RES nanoparticles demonstrated improved cellular uptake, cytotoxicity, and apoptosis compared to RES (while antioxidant activity was preserved) [ 18 ]. This led to the proposal that CD-RES nanoparticles be used as a potential inhalable delivery system for the treatment of non-small-cell-lung-cancer [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

A Brief Updated Review of Advances to Enhance Resveratrol’s Bioavailability

2021

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Resveratrol (RES) has a low bioavailability. This limitation was addressed in an earlier review and several recommendations were offered. A literature search was conducted in order to determine the extent of the research that was conducted in line with these recommendations, along with new developments in this field. Most of the identified studies were pre-clinical and confirmed the heightened activity of RES analogues compared to their parent compound. Although this has provided additional scientific kudos for these compounds and has strengthened their potential to be developed into phytopharmaceutical products, clinical trials designed to confirm this increased activity remain lacking and are warranted.

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“…For this reason, nano drug delivery system was employed here as the carrier to encapsulate resveratrol. By this way, resveratrol can be protected from being metabolized by intrinsic biological enzymes [58] and released slowly to neutral environment in vivo [59]. Human IL-13Rα2, a 380 amino acid glycoprotein located on the plasma membrane, activates tumor related signaling molecules such as PI3K, ATK and SRC to promote tumor progression [60,61].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

Xiong¹,

Lin²,

Nie³

et al. 2021

Nanotheranostics

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Background: Docetaxel and doxorubicin combination has been widely used in anaplastic thyroid cancer/ATC treatment but often results in serious adverse effects and drug resistance. Resveratrol effectively inhibits ATC cell proliferation in vitro without affecting the corresponding normal cells, while its in vivo anti-ATC effects especially on the ones with docetaxel/doxorubicin-resistance have not been reported due to its low bioavailability. Nanoparticles with sustained-release and cancer-targeting features may overcome this therapeutic bottleneck. Methods: The resveratrol nanoparticles with sustained-release and IL-13Rα2-targeting capacities (Pep-1-PEG3.5k-PCL4k@Res) were prepared to improve the in vivo resveratrol bioavailability. Human THJ-16T ATC cell line was employed to establish nude mice subcutaneous transplantation model. The tumor-bearing mice were divided into four groups as Group-1, without treatment, Group-2, treated by 30 mg/kg free resveratrol, Group-3, treated by 30 mg/kg Pep-1-PEG3.5k-PCL4k@Res and Group-4, treated by 5 mg/kg docetaxel/5 mg/kg doxorubicin combination. TUNEL staining was used to detect the apoptotic cells in the tumor tissues. Docetaxel/doxorubicin resistant xenografts named as THJ-16T/R were isolated and subjected to 2D and 3D culture. The docetaxel/doxorubicin and resveratrol sensitivities of the original THJ-16T and THJ-16T/R cells were analyzed by multiple methods. Results: Docetaxel/doxorubicin and Pep-1-PEG3.5k-PCL4k@Res but not free resveratrol significantly delayed tumor growth (P < 0.01) and caused extensive apoptosis. The mice in docetaxel/doxorubicintreated group suffered from weight loss (> 10%) and 2/3 of them died within 3 times of treatment and the chemotherapy was stop to avoid further animal loss. One week after drug withdrawal, the subcutaneous tumors regrew and the tumor volume increased 55.28% within 14 days. The cells isolated from the regrowing tumors (THJ-16T/R) were successfully cultured under 2D and 3D condition and underwent drug treatments. Compared with THJ-16T, the death rate of docetaxel/doxorubicin-treated THJ-16T/R population was lower (39.3% vs 18.0%), which remained almost unchanged in resveratrol-treated group (45.3% vs 49.3%). Conclusion: Resveratrol sustained-release targeting nanoparticles effectively inhibit in vivo ATC growth. Docetaxel/doxorubicin suppresses ATC xenografts but causes obvious side effects and secondary drug resistance that can be overcome by resveratrol.

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Inhalable resveratrol-cyclodextrin complex loaded biodegradable nanoparticles for enhanced efficacy against non-small cell lung cancer

Cited by 71 publications

References 66 publications

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

A Brief Updated Review of Advances to Enhance Resveratrol’s Bioavailability

Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

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